Studies were performed to examine the maturation and regulation of the human immune response in normal individuals and in patients with congenital and acquired immune deficiency states associated with a high frequency of cancer. The interaction of the T-cell derived lymphokine interleukin-2 (IL-2) with its cell membrane receptor (lL-2R) plays a pivotal role in the establishment and maturation of the immune response. Elevated levels of soluble IL-2R (Tac protein) were found is the serum of several retroviral associated diseases including the adult T cell leukemia (ATL), hairy cell leukemia (HCL), the acquired immune deficiency syndrome (AIDS), and patients with Kawasaki disease. Elevated serum levels of soluble Tac protein were also observed in patients with "autoimmune" disorders and patients undergoing allograft rejection episodes. Favorable responses to therapy in ATL and HCL were associated with reductions in serum Tac protein. Measurement of Tac protein in serum is thus useful in the diagnosis and management of certain cancer patients and in monitoring the state of immunologic activation in humans in vivo. In a continuing effort to define the nature of certain immunodeficiency disorders and to gain insight into human B-lymphocyte maturation, we have initiated molecular genetic studies of a kindred with X-linked hypogammaglobulinemia and isolated growth hormone deficiency. Mapping studies by restriction fragment length polymorphism have shown that this disease is due to a gene distinct from that causing the more common form of X-linked agammaglobulinemia or Bruton's disease.